15-41834741-G-T

Position:

chr15-41834741-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001114632.2(JMJD7):c.66G>T(p.Glu22Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

JMJD7
NM_001114632.2 missense, splice_region

Scores

Splicing: ADA: 0.0005221

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

JMJD7 (HGNC:34397): (jumonji domain containing 7) This gene encodes a highly conserved protein with a JmjC domain, which are part of the cupin metalloenzyme superfamily. JmjC proteins may function as 2-oxoglutarate-Fe(II)-dependent dioxygenases. Most tissues also express read-through transcripts from this gene into the downstream phospholipase A2, group IVB (cytosolic) gene, some of which may encode fusion proteins combining the N-terminus of this protein with the phospholipase A2, group IVB protein. [provided by RefSeq, Jul 2008]

JMJD7 links:

JMJD7-PLA2G4B (HGNC:):

JMJD7-PLA2G4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021177918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
JMJD7	NM_001114632.2 linkuse as main transcript	c.66G>T	p.Glu22Asp	missense_variant, splice_region_variant	2/8	ENST00000397299.9	NP_001108104.1
JMJD7-PLA2G4B	NM_005090.4 linkuse as main transcript	c.66G>T	p.Glu22Asp	missense_variant, splice_region_variant	2/25		NP_005081.1
JMJD7-PLA2G4B	NM_001198588.2 linkuse as main transcript	c.66G>T	p.Glu22Asp	missense_variant, splice_region_variant	2/24		NP_001185517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD7	ENST00000397299.9 linkuse as main transcript	c.66G>T	p.Glu22Asp	missense_variant, splice_region_variant	2/8	1	NM_001114632.2	ENSP00000380467	P1

Frequencies

GnomAD3 genomes

AF:

0.000821

AC:

125

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000785

AC:

195

AN:

248428

Hom.:

AF XY:

0.000699

AC XY:

AN XY:

134422

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00119

AC:

1742

AN:

1461556

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

835

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152326

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.000963

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000642

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00190

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.66G>T (p.E22D) alteration is located in exon 2 (coding exon 2) of the JMJD7 gene. This alteration results from a G to T substitution at nucleotide position 66, causing the glutamic acid (E) at amino acid position 22 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0077

T;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

L;.;.

MutationTaster

Benign

0.98

D;D;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.024

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0040

B;.;.

Vest4

0.16

MutPred

0.43

Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);

MVP

0.44

MPC

0.021

ClinPred

0.0069

GERP RS

3.4

Varity_R

0.24

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over